Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes

Authors


Abstract

Objectives

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes.

Design, setting and subjects

From 2009 to 2011, 667 patients with type 1 diabetes and 51 nondiabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark. suPAR levels were measured with an enzyme-linked immunosorbent assay.

Main outcome measures

The investigated diabetic complications were cardiovascular disease (CVD: previous myocardial infarction, revascularisation, peripheral arterial disease and stroke), autonomic dysfunction (heart rate variability during deep breathing <11 beats min−1), albuminuria [urinary albumin excretion rate (UAER) ≥30 mg/24 h] or a high degree of arterial stiffness (pulse wave velocity ≥10 m s−1). Analyses were adjusted for gender, age, systolic blood pressure, estimated glomerular filtration rate, UAER, glycated haemoglobin (HbA1c), total cholesterol, body mass index, C-reactive protein, antihypertensive treatment and smoking.

Results

Soluble urokinase plasminogen activator receptor levels were lower in control subjects versus all patients, in control subjects versus normoalbuminuric patients (UAER <30 mg/24 h), in normoalbuminuric patients with short (<10 years) versus long diabetes duration and were increased with degree of albuminuria (adjusted < 0.001 for all). Furthermore, suPAR levels were higher in patients with versus without CVD (= 144; 21.3%), autonomic dysfunction (= 369; 59.2%), albuminuria (= 357; 53.1%) and a high degree of arterial stiffness (= 298; 47.2%) (adjusted  0.024). The adjusted odds ratio (95% confidence interval) values per 1 ln unit increase in suPAR were as follows: 2.5 (1.1–5.7) for CVD: 2.7 (1.2–6.2) for autonomic dysfunction; 3.8 (1.3–10.9) for albuminuria and 2.5 (1.1–6.1) for a high degree of arterial stiffness ( 0.039).

Conclusion

The suPAR level is higher in patients with type 1 diabetes and is associated with diabetes duration and complications independent of other risk factors. suPAR is a potential novel risk marker for the management of diabetes.

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